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1.
J Pediatr Ophthalmol Strabismus ; : 1-8, 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38661310

RESUMEN

PURPOSE: To analyze referral rates, patient demographics, referral indications, and the impact of socioeconomic factors on ocular health from the University of California Irvine (UCI) Eye Mobile for Children, particularly during the coronavirus disease 2019 (COVID-19) pandemic. METHODS: A retrospective chart review was performed on de-identified records of children examined on the UCI Eye Mobile. GraphPad Prism 10.0.0 and Python software were used for statistical analyses. RESULTS: In the academic years from 2018 to 2022, 3,619 children received comprehensive eye examinations on the UCI Eye Mobile. Among them, 76 were referred to a pediatric ophthalmologist. The majority of these children were Hispanic (72.6%, 54 of 74), followed by Asian (10.9%, 8 of 74). A significant proportion (82.9%, 63 of 76) attended school districts with median incomes below that of Orange County. Statistically significant differences were found in age (P = .001; pre-COVID: 3.98 ± 1.08 years vs COVID: 5.75 ± 2.92 years) and gender (P = .023; pre-COVID female: 31 of 41 vs COVID female: 15 of 32) between the pre-COVID and COVID years. Additionally, there were significant differences in the proportion of children with hyperopia with astigmatism between the pre-COVID and COVID years (P = .044; pre-COVID: 23 of 40 vs COVID: 12 of 35). The most common indications for ophthalmologist referrals were for strabismus evaluation/treatment (28.9%, 22 of 76), followed by abnormal cup-to-disc ratio (21.1%, 16 of 76). CONCLUSIONS: The study highlights the pivotal role of the UCI Eye Mobile for children in identifying ocular conditions needing referrals to subspecialty care. The majority of children needing these referrals attended schools in lower economic communities. Additionally, the COVID-19 pandemic appears to have influenced the demographic and clinical characteristics. [J Pediatr Ophthalmol Strabismus. 20XX:X(X):XXX-XXX.].

2.
Commun Biol ; 7(1): 174, 2024 Feb 19.
Artículo en Inglés | MEDLINE | ID: mdl-38374434

RESUMEN

Disparities in data underlying clinical genomic interpretation is an acknowledged problem, but there is a paucity of data demonstrating it. The All of Us Research Program is collecting data including whole-genome sequences, health records, and surveys for at least a million participants with diverse ancestry and access to healthcare, representing one of the largest biomedical research repositories of its kind. Here, we examine pathogenic and likely pathogenic variants that were identified in the All of Us cohort. The European ancestry subgroup showed the highest overall rate of pathogenic variation, with 2.26% of participants having a pathogenic variant. Other ancestry groups had lower rates of pathogenic variation, including 1.62% for the African ancestry group and 1.32% in the Latino/Admixed American ancestry group. Pathogenic variants were most frequently observed in genes related to Breast/Ovarian Cancer or Hypercholesterolemia. Variant frequencies in many genes were consistent with the data from the public gnomAD database, with some notable exceptions resolved using gnomAD subsets. Differences in pathogenic variant frequency observed between ancestral groups generally indicate biases of ascertainment of knowledge about those variants, but some deviations may be indicative of differences in disease prevalence. This work will allow targeted precision medicine efforts at revealed disparities.


Asunto(s)
Predisposición Genética a la Enfermedad , Salud Poblacional , Humanos , Población Negra , Genómica , Hispánicos o Latinos/genética , Estados Unidos/epidemiología , Pueblo Europeo , Pueblo Africano
3.
J Spinal Cord Med ; : 1-13, 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38240662

RESUMEN

OBJECTIVES: (1) Examine the feasibility of a community-based exercise intervention for persons with spinal cord injury and (2) compare the cardiorespiratory fitness, skeletal muscle strength, and psychosocial well-being of participants in the intervention group versus control group. DESIGN: Community-based pilot randomized controlled trial. Setting: Accessible community-based health and wellness center. Participants: Thirty-two sedentary community-dwelling adults with any level of spinal cord injury. Interventions: Participants were randomized to a 36-session/12-week community-based exercise program (intervention; EG) or to a 36-session/12-week physical activity education group (control; CG). Outcome measures: Primary outcome measures included cardiorespiratory fitness measured by a VO2peak test, a composite score of four upper extremity musculoskeletal strength 1-repetition maximum exercises, and feasibility measured by EG participants' adherence and exercise intensity achieved during the program. EG participants' acceptance of the program was also evaluated using a self-reported satisfaction scale. Self-efficacy, motivation, pain, and goal performance and satisfaction were secondary outcome measures. Adherence and acceptability were also measured. RESULTS: Fifteen participants (n = 15) completed the community-based exercise intervention and seventeen (n = 17) completed the education program. While no statistically significant differences were found, the EG experienced changes of moderate effect size in cardiorespiratory fitness, strength, motivation, and satisfaction with their goals. The EG attended, on average, two sessions per week. The community-based exercise intervention was highly accepted by and satisfying for participants to engage in. CONCLUSIONS: The EG had improvements in the two primary measures, cardiorespiratory fitness and musculoskeletal strength, following the intervention. The community-based exercise intervention was feasible and accepted by participants.

4.
J Psychosoc Oncol ; 42(2): 256-270, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-37486181

RESUMEN

To examine the effectiveness of Mind Over Matter (MOM), a group psychosocial intervention based on CBT, ACT, and mind-body interventions, from data collected during a quality improvement project. MOM was offered in person prior to COVID-19 and via telehealth after COVID-19 began.Distress, as measured by anxiety, depression, the severity of physical symptoms and the impact of physical symptoms on daily functioning, was measured pre- and post-MOM.The sample included 46 participants with an experience of cancer ranging in age from 31 to 75.Overall, there were significant differences in anxiety, depression, and physical symptom severity and interference pre and post MOM. The in-person intervention showed significant differences in anxiety, depression, and physical symptom interference. There were significant differences in anxiety and physical symptom severity reported in the telehealth groups.MOM may be an effective psychosocial intervention for addressing cancer-related physical and emotional challenges making it a valuable resource for institutions trying to meet needs identified by distress screenings.


Asunto(s)
COVID-19 , Neoplasias , Humanos , Habilidades de Afrontamiento , Calidad de Vida , Mejoramiento de la Calidad , Neoplasias/terapia , Ansiedad/terapia , Depresión/terapia
5.
BMC Geriatr ; 23(1): 687, 2023 10 24.
Artículo en Inglés | MEDLINE | ID: mdl-37872479

RESUMEN

BACKGROUND: This study aimed to test, in real-world clinical practice, the effectiveness of a Transitional Care Stroke Intervention (TCSI) compared to usual care on health outcomes, self-management, patient experience, and health and social service use costs in older adults (≥ 55 years) with stroke and multimorbidity (≥ 2 chronic conditions). METHODS: This pragmatic randomized controlled trial (RCT) included older adults discharged from hospital to community with stroke and multimorbidity using outpatient stroke rehabilitation services in two communities in Ontario, Canada. Participants were randomized 1:1 to usual care (control group) or usual care plus the 6-month TCSI (intervention group). The TCSI was delivered virtually by an interprofessional (IP) team, and included care coordination/system navigation support, phone/video visits, monthly IP team conferences, and an online resource to support system navigation. The primary outcome was risk of hospital readmission (all cause) after six-months. Secondary outcomes included physical and mental functioning, stroke self-management, patient experience, and health and social service use costs. The intention-to-treat principle was used to conduct the primary and secondary analyses. RESULTS: Ninety participants were enrolled (44 intervention, 46 control); 11 (12%) participants were lost to follow-up, leaving 79 (39 intervention, 40 control). No significant between-group differences were seen for baseline to six-month risk of hospital readmission. Differences favouring the intervention group were seen in the following secondary outcomes: physical functioning (SF-12 PCS mean difference: 5.10; 95% CI: 1.58-8.62, p = 0.005), stroke self-management (Southampton Stroke Self-Management Questionnaire mean difference: 6.00; 95% CI: 0.51-11.50, p = 0.03), and patient experience (Person-Centred Coordinated Care Experiences Questionnaire mean difference: 2.64, 95% CI: 0.81, 4.47, p = 0.005). No between-group differences were found in total healthcare costs or other secondary outcomes. CONCLUSIONS: Although participation in the TCSI did not impact hospital readmissions, there were improvements in physical functioning, stroke self-management and patient experience in older adults with stroke and multimorbidity without increasing total healthcare costs. Challenges associated with the COVID-19 pandemic, including the shift from in-person to virtual delivery, and re-deployment of interventionists could have influenced the results. A larger pragmatic RCT is needed to determine intervention effectiveness in diverse geographic settings and ethno-cultural populations and examine intervention scalability. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT04278794 . Registered May 2, 2020.


Asunto(s)
Accidente Cerebrovascular , Cuidado de Transición , Anciano , Humanos , Multimorbilidad , Ontario/epidemiología , Calidad de Vida , Accidente Cerebrovascular/diagnóstico , Accidente Cerebrovascular/epidemiología , Accidente Cerebrovascular/terapia
6.
Clin Transl Radiat Oncol ; 42: 100667, 2023 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-37560324

RESUMEN

Background and Purpose: With the growing interest in total neoadjuvant treatment for locally advanced rectal adenocarcinoma (LARC) there is an urgent unmet need to identify predictive markers of response to long-course neoadjuvant concurrent chemoradiotherapy (LCRT). O6-Methylguanine (O6-MG)-DNA-methyltransferase (MGMT) gene methylation has been associated in some malignancies with response to concurrent chemoradiotherapy. We attempted to find if pathologic response to LCRT was associated with MGMT promoter hypermethylation (MGMTh). Materials and Methods: Patients were identified with LARC, available pre-treatment biopsy specimens, and at least 1 year of follow-up who received LCRT followed by surgical resection within 6 months. Biopsies were tested for MGMTh using a Qiagen pyrosequencing kit (Catalog number 970061). The primary outcome of LCRT responsiveness was based on tumor regression grade (TRG), with grades of 0-1 considered to have excellent response and grades of 2-3 considered to be non-responders. Secondary outcomes included overall survival (OS) and recurrence free survival (RFS). Results: Of 96 patients who met inclusion criteria, 76 had samples which produced reliable assay results. MGMTh corresponded with higher grade and age of the biopsy specimen. The percentage of responders to LCRT was higher amongst the MGMTh patients than the MGMTn patients (60.0% vs 27.5%, p value = 0.0061). MGMTh was not significantly associated with improved OS (2-year OS of 96.0% vs 98.0%, p = 0.8102) but there was a trend for improved RFS (2-year RFS of 87.6% vs 74.2%, p = 0.0903). Conclusion: Significantly greater tumor regression following LCRT was seen in MGMTh LARC. Methylation status may help identify good candidates for close observation without surgery following LCRT.

7.
Sci Rep ; 13(1): 12618, 2023 08 03.
Artículo en Inglés | MEDLINE | ID: mdl-37537263

RESUMEN

Due to multi-drug resistance, physicians increasingly use the last-resort antibiotic colistin to treat infections with the Gram-negative bacterium Klebsiella pneumoniae. Unfortunately, K. pneumoniae can also develop colistin resistance. Interestingly, colistin resistance has dual effects on bacterial clearance by the immune system. While it increases resistance to antimicrobial peptides, colistin resistance has been reported to sensitize certain bacteria for killing by human serum. Here we investigate the mechanisms underlying this increased serum sensitivity, focusing on human complement which kills Gram-negatives via membrane attack complex (MAC) pores. Using in vitro evolved colistin resistant strains and a fluorescent MAC-mediated permeabilization assay, we showed that two of the three tested colistin resistant strains, Kp209_CSTR and Kp257_CSTR, were sensitized to MAC. Transcriptomic and mechanistic analyses focusing on Kp209_CSTR revealed that a mutation in the phoQ gene locked PhoQ in an active state, making Kp209_CSTR colistin resistant and MAC sensitive. Detailed immunological assays showed that complement activation on Kp209_CSTR in human serum required specific IgM antibodies that bound Kp209_CSTR but did not recognize the wild-type strain. Together, our results show that developing colistin resistance affected recognition of Kp209_CSTR and its killing by the immune system.


Asunto(s)
Colistina , Infecciones por Klebsiella , Humanos , Colistina/farmacología , Colistina/uso terapéutico , Klebsiella pneumoniae/genética , Proteínas Bacterianas/farmacología , Farmacorresistencia Bacteriana/genética , Antibacterianos/farmacología , Antibacterianos/uso terapéutico , Mutación , Inmunoglobulina M/genética , Infecciones por Klebsiella/tratamiento farmacológico , Infecciones por Klebsiella/microbiología , Pruebas de Sensibilidad Microbiana
8.
Optom Vis Sci ; 100(7): 432-443, 2023 Jul 01.
Artículo en Inglés | MEDLINE | ID: mdl-37399233

RESUMEN

SIGNIFICANCE: This pilot randomized trial, the first to evaluate a specific base-in relieving prism treatment strategy for childhood intermittent exotropia, did not support proceeding to a full-scale clinical trial. Defining and measuring prism adaptation in children with intermittent exotropia are challenging and need further study. PURPOSE: This study aimed to determine whether to proceed to a full-scale trial of relieving base-in prism spectacles versus refractive correction alone for children with intermittent exotropia. METHODS: Children 3 years old to those younger than 13 years with distance intermittent exotropia control score of ≥2 points on the Intermittent Exotropia Office Control Scale (Strabismus 2006;14:147-150; 0 [phoria] to 5 [constant]), ≥1 episode of spontaneous exotropia, and 16 to 35∆ by prism-and-alternate-cover test, who did not fully prism adapt on a 30-minute in-office prism-adaptation test were randomized to base-in relieving prism (40% of the larger of distance and near exodeviations) or nonprism spectacles for 8 weeks. A priori criteria to conduct a full-scale trial were defined for the adjusted treatment group difference in mean distance control: "proceed" (≥0.75 points favoring prism), "uncertain" (>0 to <0.75 points favoring prism), or "do not proceed" (≥0 points favoring nonprism). RESULTS: Fifty-seven children (mean age, 6.6 ± 2.2 years; mean baseline distance control, 3.5 points) received prism (n = 28) or nonprism (n = 29) spectacles. At 8 weeks, mean control values were 3.6 and 3.3 points in prism (n = 25) and nonprism (n = 25) groups, respectively, with an adjusted difference of 0.3 points (95% confidence interval, -0.5 to 1.1 points) favoring nonprism (meeting our a priori "do not proceed" criterion). CONCLUSIONS: Base-in prism spectacles, equal to 40% of the larger of the exodeviations at distance or near, worn for 8 weeks by 3- to 12-year-old children with intermittent exotropia did not yield better distance control than refractive correction alone, with the confidence interval indicating that a favorable effect of 0.75 points or larger is unlikely. There was insufficient evidence to warrant a full-scale randomized trial.


Asunto(s)
Exotropía , Niño , Humanos , Preescolar , Exotropía/terapia , Anteojos , Proyectos Piloto , Refracción Ocular , Pruebas de Visión
9.
mBio ; 14(3): e0080023, 2023 06 27.
Artículo en Inglés | MEDLINE | ID: mdl-37140436

RESUMEN

Klebsiella pneumoniae is a leading cause of nosocomial infections, including pneumonia, bacteremia, and urinary tract infections. Treatment options are increasingly restricted by the high prevalence of resistance to frontline antibiotics, including carbapenems, and the recently identified plasmid-conferred colistin resistance. The classical pathotype (cKp) is responsible for most of the nosocomial infections observed globally, and these isolates are often multidrug resistant. The hypervirulent pathotype (hvKp) is a primary pathogen capable of causing community-acquired infections in immunocompetent hosts. The hypermucoviscosity (HMV) phenotype is strongly associated with the increased virulence of hvKp isolates. Recent studies demonstrated that HMV requires capsule (CPS) synthesis and the small protein RmpD but is not dependent on the increased amount of capsule associated with hvKp. Here, we identified the structure of the capsular and extracellular polysaccharide isolated from hvKp strain KPPR1S (serotype K2) with and without RmpD. We found that the polymer repeat unit structure is the same in both strains and that it is identical to the K2 capsule. However, the chain length of CPS produced by strains expressing rmpD demonstrates more uniform length. This property was reconstituted in CPS from Escherichia coli isolates that possess the same CPS biosynthesis pathway as K. pneumoniae but naturally lack rmpD. Furthermore, we demonstrate that RmpD binds Wzc, a conserved capsule biosynthesis protein required for CPS polymerization and export. Based on these observations, we present a model for how the interaction of RmpD with Wzc could impact CPS chain length and HMV. IMPORTANCE Infections caused by Klebsiella pneumoniae continue to be a global public health threat; the treatment of these infections is complicated by the high frequency of multidrug resistance. K. pneumoniae produces a polysaccharide capsule required for virulence. Hypervirulent isolates also have a hypermucoviscous (HMV) phenotype that increases virulence, and we recently demonstrated that a horizontally acquired gene, rmpD, is required for HMV and hypervirulence but that the identity of the polymeric product(s) in HMV isolates is uncertain. Here, we demonstrate that RmpD regulates capsule chain length and interacts with Wzc, a part of the capsule polymerization and export machinery shared by many pathogens. We further show that RmpD confers HMV and regulates capsule chain length in a heterologous host (E. coli). As Wzc is a conserved protein found in many pathogens, it is possible that RmpD-mediated HMV and increased virulence may not be restricted to K. pneumoniae.


Asunto(s)
Infección Hospitalaria , Infecciones por Klebsiella , Humanos , Escherichia coli , Virulencia/genética , Factores de Virulencia/genética , Klebsiella pneumoniae , Antibacterianos , Polisacáridos , Infecciones por Klebsiella/epidemiología
10.
J Community Health ; 48(3): 528-538, 2023 06.
Artículo en Inglés | MEDLINE | ID: mdl-36745356

RESUMEN

State vaccine requirements are a tool for improving child and adolescent vaccination immunization coverage, but to be effective, parental buy-in is needed. The objective of this study was to assess the demographic, healthcare characteristics, and health beliefs associated with parental acceptance of general and HPV-specific state vaccine requirements. Indiana parents (N = 601) with children ages 11-17 years old completed a survey during March 2020.Results showed that 47.2% and 43.1% of parents believed there should always be general and HPV-specific state vaccine requirements, respectively. In multivariable analysis, higher odds of parental support for general state vaccine requirements were associated with being unsure whether HPV-associated cancer is a problem in the participant's county and having higher perceived benefits of HPV vaccines. Lower odds were associated with private insurance, having less than a bachelor's degree, and having less confidence in vaccines. In comparison, parents had higher odds of agreeing with HPV-specific state vaccine requirements if they reported higher interpersonal altruism and higher perceived benefits of HPV vaccines; they had lower odds if they were non-Hispanic White. Findings indicate that while similar percentages of parents agreed with general and HPV-specific state vaccine requirements, there were different characteristics associated with acceptance of each. Results can inform the development of tailored interventions for improving parental support for general and HPV-specific state vaccine requirements.


Asunto(s)
Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Adolescente , Niño , Humanos , Vacunas contra Papillomavirus/uso terapéutico , Indiana , Infecciones por Papillomavirus/prevención & control , Aceptación de la Atención de Salud , Conocimientos, Actitudes y Práctica en Salud , Padres , Vacunación , Encuestas y Cuestionarios
11.
Gen Dent ; 71(1): 38-43, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36592357

RESUMEN

Oropharyngeal cancer (OPC) has the highest incidence of any cancer caused by human papillomavirus (HPV). Oral health providers are urged to support the use of the HPV vaccine, which was approved by the US Food and Drug Administration for the prevention of OPC in 2020. This study evaluated the preferences of dental patients regarding 11 modalities for learning about HPV-related topics from their oral health providers. An online survey was administered to US adults aged 18 to 45 years (n = 285) to assess their communication modality preferences, prior experience discussing HPV with oral health providers, and demographic characteristics. Multiple items were combined to obtain preference scores for each modality. Preference scores were compared using 2 × 3 mixed analysis of variance. Age, sex, income, and HPV vaccination status were assessed as potential confounders. One-on-one discussions were the most preferred modality for learning about HPV-related topics; however, the preference scores differed based on whether the patient had prior HPV-related discussions with oral health providers (partial η2 = 0.054). Patients who had prior discussions showed a weaker preference for one-on-one discussions than did patients who had not had prior discussions. Oral health providers are called on to promote HPV vaccination, which will require increasing communication on this subject with patients. To assure greater acceptance of their recommendations, providers will need to match their communication styles to those desired by their patients. As part of a comprehensive HPV prevention strategy that includes administration of the vaccine, oral health providers should be educated on how to confidently discuss HPV-related issues with their patients.


Asunto(s)
Neoplasias Orofaríngeas , Infecciones por Papillomavirus , Vacunas contra Papillomavirus , Humanos , Virus del Papiloma Humano , Infecciones por Papillomavirus/complicaciones , Infecciones por Papillomavirus/prevención & control , Vacunación , Comunicación , Vacunas contra Papillomavirus/uso terapéutico , Conocimientos, Actitudes y Práctica en Salud
12.
F1000Res ; 11: 530, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36262335

RESUMEN

In October 2021, 59 scientists from 14 countries and 13 U.S. states collaborated virtually in the Third Annual Baylor College of Medicine & DNANexus Structural Variation hackathon. The goal of the hackathon was to advance research on structural variants (SVs) by prototyping and iterating on open-source software. This led to nine hackathon projects focused on diverse genomics research interests, including various SV discovery and genotyping methods, SV sequence reconstruction, and clinically relevant structural variation, including SARS-CoV-2 variants. Repositories for the projects that participated in the hackathon are available at https://github.com/collaborativebioinformatics.


Asunto(s)
COVID-19 , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , Genómica , Programas Informáticos
13.
JMIR Infodemiology ; 2(1): e34231, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35814809

RESUMEN

Background: Since COVID-19 vaccines became broadly available to the adult population, sharp divergences in uptake have emerged along partisan lines. Researchers have indicated a polarized social media presence contributing to the spread of mis- or disinformation as being responsible for these growing partisan gaps in uptake. Objective: The major aim of this study was to investigate the role of influential actors in the context of the community structures and discourse related to COVID-19 vaccine conversations on Twitter that emerged prior to the vaccine rollout to the general population and discuss implications for vaccine promotion and policy. Methods: We collected tweets on COVID-19 between July 1, 2020, and July 31, 2020, a time when attitudes toward the vaccines were forming but before the vaccines were widely available to the public. Using network analysis, we identified different naturally emerging Twitter communities based on their internal information sharing. A PageRank algorithm was used to quantitively measure the level of "influentialness" of Twitter accounts and identifying the "influencers," followed by coding them into different actor categories. Inductive coding was conducted to describe discourses shared in each of the 7 communities. Results: Twitter vaccine conversations were highly polarized, with different actors occupying separate "clusters." The antivaccine cluster was the most densely connected group. Among the 100 most influential actors, medical experts were outnumbered both by partisan actors and by activist vaccine skeptics or conspiracy theorists. Scientists and medical actors were largely absent from the conservative network, and antivaccine sentiment was especially salient among actors on the political right. Conversations related to COVID-19 vaccines were highly polarized along partisan lines, with "trust" in vaccines being manipulated to the political advantage of partisan actors. Conclusions: These findings are informative for designing improved vaccine information communication strategies to be delivered on social media especially by incorporating influential actors. Although polarization and echo chamber effect are not new in political conversations in social media, it was concerning to observe these in health conversations on COVID-19 vaccines during the vaccine development process.

14.
Soc Sci Med ; 301: 114934, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35378429

RESUMEN

In this critical ethnographic study, we examined women's end of life experiences in Malawi, one of the few countries in the world with a national palliative care policy. Specifically, we explored how women's and their caregivers' experiences were shaped by family and community care, and material needs. Interviews and observations with female clients of a non-governmental organization in rural Central Malawi, and with their caregivers, revealed that community-level support was both precarious and critical. We found three main themes: (1) I stay with them well, (2) we eat together, and (3) everyone is for themselves. The analysis illustrates the centrality of community care, social in/exclusion, and availability of stable food, shelter, medical, and caregiving resources on health and wellbeing at end of life. We provide recommendations to strengthen community care opportunities and women's resource bases.


Asunto(s)
Población Rural , Salud de la Mujer , Muerte , Femenino , Humanos , Malaui , Cuidados Paliativos
15.
Genome Med ; 14(1): 34, 2022 03 28.
Artículo en Inglés | MEDLINE | ID: mdl-35346344

RESUMEN

BACKGROUND: The All of Us Research Program (AoURP, "the program") is an initiative, sponsored by the National Institutes of Health (NIH), that aims to enroll one million people (or more) across the USA. Through repeated engagement of participants, a research resource is being created to enable a variety of future observational and interventional studies. The program has also committed to genomic data generation and returning important health-related information to participants. METHODS: Whole-genome sequencing (WGS), variant calling processes, data interpretation, and return-of-results procedures had to be created and receive an Investigational Device Exemption (IDE) from the United States Food and Drug Administration (FDA). The performance of the entire workflow was assessed through the largest known cross-center, WGS-based, validation activity that was refined iteratively through interactions with the FDA over many months. RESULTS: The accuracy and precision of the WGS process as a device for the return of certain health-related genomic results was determined to be sufficient, and an IDE was granted. CONCLUSIONS: We present here both the process of navigating the IDE application process with the FDA and the results of the validation study as a guide to future projects which may need to follow a similar path. Changes to the program in the future will be covered in supplementary submissions to the IDE and will support additional variant classes, sample types, and any expansion to the reportable regions.


Asunto(s)
Farmacogenética , Salud Poblacional , Genómica , Humanos , Estados Unidos , Secuenciación Completa del Genoma/métodos
16.
Genet Med ; 24(5): 1062-1072, 2022 05.
Artículo en Inglés | MEDLINE | ID: mdl-35331649

RESUMEN

PURPOSE: The Mayo-Baylor RIGHT 10K Study enabled preemptive, sequence-based pharmacogenomics (PGx)-driven drug prescribing practices in routine clinical care within a large cohort. We also generated the tools and resources necessary for clinical PGx implementation and identified challenges that need to be overcome. Furthermore, we measured the frequency of both common genetic variation for which clinical guidelines already exist and rare variation that could be detected by DNA sequencing, rather than genotyping. METHODS: Targeted oligonucleotide-capture sequencing of 77 pharmacogenes was performed using DNA from 10,077 consented Mayo Clinic Biobank volunteers. The resulting predicted drug response-related phenotypes for 13 genes, including CYP2D6 and HLA, affecting 21 drug-gene pairs, were deposited preemptively in the Mayo electronic health record. RESULTS: For the 13 pharmacogenes of interest, the genomes of 79% of participants carried clinically actionable variants in 3 or more genes, and DNA sequencing identified an average of 3.3 additional conservatively predicted deleterious variants that would not have been evident using genotyping. CONCLUSION: Implementation of preemptive rather than reactive and sequence-based rather than genotype-based PGx prescribing revealed nearly universal patient applicability and required integrated institution-wide resources to fully realize individualized drug therapy and to show more efficient use of health care resources.


Asunto(s)
Citocromo P-450 CYP2D6 , Farmacogenética , Centros Médicos Académicos , Secuencia de Bases , Citocromo P-450 CYP2D6/genética , Genotipo , Humanos , Farmacogenética/métodos
17.
Am J Emerg Med ; 53: 163-167, 2022 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-35063887

RESUMEN

OBJECTIVE: We developed a clinical tool comprising patient risk factors for having an abnormal calcium (Ca), magnesium (Mg) or phosphate (PO4) level. We hypothesized that patients without a risk factor do not require testing. This study examined the tool's potential utility for rationalizing Ca, Mg and PO4 ordering in the emergency department (ED). METHODS: We undertook a retrospective observational study in a single metropolitan ED. Patients aged 18 years or more who presented between July and December 2019 were included if they had a Ca, Mg or PO4 test during their ED stay. Demographic and clinical data, including the presence of risk factors, were extracted from the medical record. The primary outcome was a clinically significant abnormal Ca, Mg or PO4 level (>0.2 mmol/l above or below the laboratory reference range). RESULTS: Calcium, Mg and PO4 levels were measured on 1426, 1296 and 1099 patients, respectively. The positive and negative predictive values and likelihood ratios of the tool identifying a patient with a Ca level > 0.2 mmol/l outside the range were 0.05, 0.99, 1.59 and 0.41, respectively. The values for Mg were 0.02, 1.00, 1.44 and 0.35 and those for PO4 were 0.15, 0.93, 1.38 and 0.57, respectively. The majority of patients not identified as having an abnormal level did not receive electrolyte correction treatment. Application of the tool would have resulted in a 35.8% cost reduction. CONCLUSION: The tool failed to predict a very small proportion of patients (approximately 1%) with an abnormal Ca or Mg level and for whom it would have been desirable to have these levels measured. It may help rationalize Ca and Mg ordering and reduce laboratory costs.


Asunto(s)
Calcio , Magnesio , Adolescente , Servicio de Urgencia en Hospital , Humanos , Fosfatos , Estudios Retrospectivos
18.
Emerg Med J ; 39(4): 325-330, 2022 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-34706898

RESUMEN

BACKGROUND: To compare the clinical and demographic variables of patients who present to the ED at different times of the day in order to determine the nature and extent of potential selection bias inherent in convenience sampling METHODS: We undertook a retrospective, observational study of data routinely collected in five EDs in 2019. Adult patients (aged ≥18 years) who presented with abdominal or chest pain, headache or dyspnoea were enrolled. For each patient group, the discharge diagnoses (primary outcome) of patients who presented during the day (08:00-15:59), evening (16:00-23:59), and night (00:00-07:59) were compared. Demographics, triage category and pain score, and initial vital signs were also compared. RESULTS: 2500 patients were enrolled in each of the four patient groups. For patients with abdominal pain, the diagnoses differed significantly across the time periods (p<0.001) with greater proportions of unspecified/unknown cause diagnoses in the evening (47.4%) compared with the morning (41.7%). For patients with chest pain, heart rate differed (p<0.001) with a mean rate higher in the evening (80 beats/minute) than at night (76). For patients with headache, mean patient age differed (p=0.004) with a greater age in the daytime (46 years) than the evening (41). For patients with dyspnoea, discharge diagnoses differed (p<0.001). Asthma diagnoses were more common at night (12.6%) than during the daytime (7.5%). For patients with dyspnoea, there were also differences in gender distribution (p=0.003), age (p<0.001) and respiratory rates (p=0.003) across the time periods. For each patient group, the departure status differed across the time periods (p<0.001). CONCLUSION: Patients with abdominal or chest pain, headache or dyspnoea differ in a range of clinical and demographic variables depending upon their time of presentation. These differences may potentially introduce selection bias impacting upon the internal validity of a study if convenience sampling of patients is undertaken.


Asunto(s)
Dolor en el Pecho , Servicio de Urgencia en Hospital , Adolescente , Adulto , Dolor en el Pecho/diagnóstico , Dolor en el Pecho/etiología , Humanos , Persona de Mediana Edad , Estudios Retrospectivos , Sesgo de Selección , Triaje
19.
J Med Virol ; 94(3): 937-944, 2022 03.
Artículo en Inglés | MEDLINE | ID: mdl-34596257

RESUMEN

As surges in the COVID-19 pandemic have continued worldwide, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has mutated, spawning several new variants, and impacting, to various degrees, transmission, disease severity, diagnostics, therapeutics, and natural and vaccine-induced immunity. Baylor Scott & White Health has implemented, along with laboratory diagnosis, SARS-CoV-2 sequencing to identify variants in its geographical service area. We analyzed virus sequencing results of specimens collected across Central Texas and found dramatic changes in variant distribution in the first half of 2021. The alpha variant (B 1.1.7) became predominant at week 13 and continued dominance until week 25. A growth rate of 1.20 (R2 = 0.92) for the first 15 weeks was noted and this growth gradually declined to -0.55 (R2 = 0.99) for the final 13 weeks. Currently, B.1.1.7 is being displaced with B.1.617.2 at a 0.58 growth rate (R2 = 0.97). We also investigated vaccine breakthrough cases (VBCs) within our healthcare system and present clinical data on 28 symptomatic patients.


Asunto(s)
COVID-19 , Vacunas , COVID-19/diagnóstico , COVID-19/epidemiología , COVID-19/prevención & control , Vacunas contra la COVID-19 , Humanos , Pandemias , SARS-CoV-2/genética , Texas/epidemiología
20.
Health Commun ; 37(7): 919-921, 2022 06.
Artículo en Inglés | MEDLINE | ID: mdl-33427513

RESUMEN

The COVID-19 pandemic is shining a light on altruistic behaviors needed to prevent the spread of the virus. This short essay presents a personal experience of altruism during the COVID-19 pandemic and its resulting motivation to leverage it in health behavior change strategies for vaccination and other pandemic protective behaviors.


Asunto(s)
COVID-19 , Altruismo , COVID-19/epidemiología , Humanos , Motivación , Pandemias , Vacunación
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